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Pulmonary oedema with multiple sclerosis R Summerfield MA MB N Tubridy MD MRCP A Sirker MB MRCP 1 N R Banner BM FRCP 1 R C Peatfield MD FRCP J R Soc Med 2002;95:401–402
Pulmonary oedema is a well recognized complication of various neurological disorders but has seldom been reported in multiple sclerosis. CASE HISTORY
A previously healthy woman of 46 became acutely dyspnoeic, without chest pain or palpitations. Two days earlier she had noted mild ankle swelling. On admission, heart rate was 110/min, respiratory rate 25 /min and blood pressure 100/60 mmHg. A 12-lead electrocardiogram (ECG) showed ST depression in the lateral chest leads but no Q-waves or other evidence of acute myocardial infarction. A chest X-ray revealed generalized pulmonary oedema with bilateral small pleural effusions (Figure 1). There was no evidence of infection and a ventilationperfusion scan was normal. An echocardiogram showed an akinetic intraventricular septum and anterior left ventricle wall with ejection fraction (EF) 39%. There was a small posterior pericardial effusion. It was noted that the basal and anterior wall impairment did not conform with standard coronary anatomy. Believed to be in cardiogenic shock, she was transferred to Harefield Hospital in case mechanical circulatory support became necessary. With intravenous inotropes and diuretics her condition improved; an angiotensin converting-enzyme inhibitor was introduced and the inotropic support was gradually tapered off. A coronary angiogram demonstrated normal coronary vasculature. Clinically, she made an excellent recovery, and myocardial recovery was likewise rapid: six days after the initial echocardiogram the EF had risen to 55% and on discharge 3 weeks later it was 69%. While in hospital, the patient complained of a constant tingling in both hands and intermittent slurring of speech. She had no numbness or weakness and there was no reported visual or sphincter disturbance. On further inquiry she revealed that, in the week before admission, she had had an episode of visual disturbance: when driving, everything
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had appeared to be ‘moving up and down’. The effect was binocular and not affected by the direction of gaze. After two days this had subsided spontaneously. She also recalled neurological symptoms 10 years previously. She had woken one morning with weakness in the left arm and leg and poor coordination which caused her to fall over twice. At that time her leg and arm, but not her face, were numb and her speech was slurred as now. The symptoms resolved over a few days. Visual evoked potentials (VEPs) and a CT brain study were normal. 2 years before the current admission she had had paroxysms of head pain radiating to her left arm and associated with slurred speech but no limb weakness. More recently she had complained of similar pains in the right side of the head for several months. There was no history of Lhermitte’s phenomenon. On neurological examination there were no objective abnormalities. Routine blood and biochemistry results were normal. The VEPs were still within normal limits but the cerebrospinal fluid (CSF) showed oligoclonal bands which were not matched in serum. An MRI brain study showed diffuse periventricular white matter changes consistent with multiple sclerosis. There were similar lesions in the brainstem and cerebellum (Figure 2) and in particular there was a large enhancing lesion in the medulla, in the region of the nucleus tractus solitarius.
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The neurological conditions that can be complicated by pulmonary oedema include subarachnoid haemorrhage, seizures, head injury, stroke, bulbar poliomyelitis and acute hydrocephalus1,2. There are few case studies of pulmonary oedema in patients with brainstem demyelination. Melin et al.2 reviewed the published work and noted that the pulmonary oedema was commonly preceded (by some weeks) by diffuse brainstem neurological symptoms such as dizziness, ataxia and paraesthesia. In one report the patient,
Department of Neuroscience, Charing Cross Hospital, Fulham Palace Road, London W6 8RF; 1Department of Cardiology and Transplant Medicine, Harefield Hospital, Middlesex UB9 6JH, UK Correspondence to: Dr R Peatfield E-mail:
[email protected]
Figure 1 Chest X-ray on admission. The radiograph shows perihilar air space shadowing consistent with severe pulmonary oedema secondary to acute left ventricular dysfunction. There is no cardiomegaly
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Initially we thought that our patient might be having multiple cerebrovascular episodes, so we started her on warfarin and arranged a coronary angiogram. A CT scan was uninformative. It was early MR imaging that yielded the diagnosis. REFERENCES
Figure 2
Brainstem demyelinating plaque in the region of the nucleus tractus solitarius
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like ours, had a preceding episode of oscillopsia. ECG findings are variable and non-specific although intermittent atrial fibrillation has been described3. Echocardiographic indices, when reported, have been judged normal, though patients were studied after the abnormal findings had largely resolved3,4. Similarly with MRI, few studies have been performed in the acute stage of disease1. What is the mechanism of neurogenic pulmonary oedema? One theory is that lesions in the preoptic hypothalamus, or diffuse intracranial hypertension, affect the medullary autonomic pathways, inducing bradycardia and hypertension5,6; MRI studies suggest an area in or near the nucleus of tractus solitarius (NTS) as the more likely origin1. A lesion in the caudal medulla adjacent to the obex has been described in two patients with multiple sclerosis and pulmonary oedema1,2. The authors point out that efferent signals from the NTS terminate in the thoracic spinal cord and that lesions of the NTS in laboratory animals have generated increases in pulmonary arterial pressure in the absence of a rise in systemic and left atrial pressures. Increased intravascular pressures in the lung, they speculate, would result in unbalanced precardiac and postcardiac loads, leading to fluid movement into the alveolar spaces. In the largest single series of patients in which pulmonary oedema fluid was evaluated, the primary mechanism was believed to be hydrostatic7. This contrasts with a previously suggested mechanism of increased pulmonary capillary permeability8,9. The lesion in the region of the NTS in the medulla of our patient supports the idea that this is the key site. But in addition, at least part of the mechanism was the left ventricular dysfunction and a consequent rise in pulmonary capillary wedge pressure.
1 Simon RP, Gean-Martin AD, Sander JE. Medullary lesion inducing pulmonary edema: a magnetic resonance imaging study. Ann Neurol 1991;30:727–30 2 Melin J, Usenius JP, Fogelholm R. Left ventricular failure and pulmonary edema in acute multiple sclerosis. Acta Neurol Scand 1996; 93:315–17 3 Schroth WS, Tenner SM, Rappaport BA, Mani R. Multiple sclerosis as a cause of atrial fibrillation and echocardiographic changes. Arch Neurol 1992;49:422–4 4 Gentolini N, Schavino D, Della Corte F, Ricci E, Colosimo C. Neurogenic pulmonary edema: a presenting symptom in multiple sclerosis. Ital J Neurol Sci 1992;13:435–8 5 Marie FW, Patton HD. Neural structures involved in the genesis of ‘preoptic pulmonary edema,’ gastric erosions and behavior changes. Am J Physiol 1956;184:345–50 6 Ducker TB. Increased intracranial pressure and pulmonary edema. Part 1: clinical study of 11 patients. J Neurosurg 1968;28:112–17 7 Smith WS, Mathay MA. Evidence for a hydrostatic mechanism in human neurogenic edema. Chest 1997;111:1326–33 8 Theodore J, Robin ED. Speculations on neurogenic pulmonary edema. Am Rev Resp Dis 1976;113:404–11 9 Lagerkranser M, Pehrsson K, Sylven C. Neurogenic pulmonary oedema. A review of the pathophysiology with clinical and therapeutic implications. Acta Med Scand 1982;212:267–71 10 Poser CM, Paty DW, Scheinberg, et al. New diagnostic criteria for multiple sclerosis: guidelines for reasearch protocols. Ann Neurol 1983; 13:227–31
Nose-bleeds after sildenafil (Viagra) L A Hicklin FRCS(Orl) C Ryan MRCS D K K Wong MRCS A E Hinton FRCS(Orl) J R Soc Med 2002;95:402–403
Sildenafil (Viagra) enhances penile erection by relaxing smooth muscle in the corpus cavernosum. Erectile tissues elsewhere may be affected by this drug. CASE HISTORIES
Case 1
A man in his late 50s was admitted from the emergency department with heavy prolonged epistaxis. Attempts to Department of Otolaryngology, St George’s Hospital, Blackshaw Road, London SW17 0QT, UK Correspondence to: L A Hicklin E-mail:
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control the bleeding with cautery, sponge packs and BIPP (bismuth iodoform paraffin paste) impregnated gauze had been unsuccessful. Haemostasis was eventually secured with bilateral postnasal space balloons and anterior BIPP gauze packing. There was a history of hypertension, well controlled with nifedipine and lisinopril. During the admission the patient volunteered that, in the hours before his first nose-bleed, he had been engaging in energetic sexual activity. To enhance his sexual performance he had taken 50 mg sildenafil. Over the subsequent few days he had had several short but heavy epistaxes, and on the day of admission bleeding had continued for 6 hours without stopping. With packing and bed rest the bleeding gradually settled and he was discharged after six days.
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Profound hypokalaemia in a patient with Creutzfeldt–Jakob disease Abdelnassir M Abdelgabar MRCP J R Soc Med 2002;95:403–404
In Creutzfeldt–Jakob disease (CJD) routine biochemical tests are usually within normal limits. A few patients have had slight increases in liver enzymes and bilirubin, or persistent hypercalcaemia1. Hypokalaemia does not seem to have been reported.
Case 2
A man in his early 70s was admitted from the emergency department after 5 hours of epistaxis. He had taken sildenafil to enhance his sexual performance in the morning before his epistaxis. Haemostasis was secured with bilateral BIPP packing. This was his first nose-bleed requiring medical attention. His history included hypertension well controlled with amlodipine. The pack was removed after two days and he was discharged home with no further epistaxis. COMMENT
Severe epistaxis particularly affects the elderly, people with hypertension or clotting disorders and those taking medications such as aspirin or warfarin1. Venous engorgement is believed to be a causal factor2. The turbinates of the nose contain erectile tissue3 and nasal stuffiness during sexual activity is a well known phenomenon (‘honeymoon rhinitis’)4. Nasal stuffiness is also listed as a side-effect of sildenafil5. In the two patients here we surmise that venous engorgement due to sildenafil was a factor in the severe epistaxes after sexual activity. This phenomenon does not seem to have been reported elsewhere. There has been no obvious increase in epistaxis since the introduction of sildenafil; this effect, however, might be under-reported because of the disinclination of most patients to discuss sexual matters in public, especially those relating to sexual dysfunction. REFERENCES
1 Tan LKS, Calhoun KH. Epistaxis. Med Clin N Am 1999;83:45–56 2 Mackay IS, Bull TR. Rhinology. In: Kerr AG, ed. Scott-Brown’s Otolaryngology, Vol. 4. Oxford: Butterworth-Heinemann, 1997:18:5–7 3 Stammberger H. The nose. In: Hawke M, ed. A Colour Atlas of Otolaryngology. London: Martin Dunitz, 1995:89 4 Mackay IS. Rhinitis and sinusitis. Br J Dis Chest 1988;82:1–8 5 Anonymous. Viagra (Sildenafil) Data Sheet. Sandwich: Pfizer Ltd, 2000
CASE HISTORY
A man aged 79 was admitted after four weeks of progressive unsteadiness and intermittent diplopia. His only medication was nifedipine for hypertension. He was fully oriented and coherent, and examination of the nervous system revealed only mild incoordination of the left arm and hyporeflexia. Sensation was normal, there was no wasting, and fasciculation and myoclonus were absent. All haematological and biochemical tests were normal apart from a slightly depressed potassium (3.4 mmol/L). Subsequent examination of case notes indicated a similar plasma potassium a year previously, when the patient had a knee replacement. A brain MRI scan showed only age-related ischaemic changes. Within two weeks from admission the patient became grossly ataxic and was intermittently confused; myoclonic jerks were observed. A neurologist raised the possibility of CJD and he was transferred to the regional neurology centre for the appropriate tests. The electroencephalogram was not typical of CJD, but cerebrospinal fluid was positive for the brain specific protein 14-3-3; also, S100b was high at 2.99 ng/mL (normal 50.38). Autoantibody screening, including ganglioside and cerebellum antibodies (Purkinje and neuronal), was negative. Genetic testing showed the patient to be valine homozygous at codon 129 of the prion protein gene with no apparent mutations; this rules out familial CJD. The patient deteriorated to frank dementia and akinetic mutism within two months. Apart from the neurological deterioration, a striking feature was of progressive hypokalaemia, with potassium as low as 2.2 mmol/L despite oral supplements. This refractory hypokalaemia was complicated by several episodes of bowel pseudo-obstruction and of Princess of Wales Hospital, Grimsby DN33 2BA, UK E-mail:
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Box 1 Diagnostic criteria for sporadic CJD (from Ref. 2) 1 Rapidly progressive dementia 2 (A) Myoclonus (B) Visual or cerebellar problems (C) Pyramidal or extrapyramidal features (D) Akinetic mutism 3 Typical electroencephalogram . Definite=neuropathological/immunocytochemically confirmed . Probable=1+two of 2+3 or possible+positive protein 14-3-3 . Possible=1+two of 2+duration52 years
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Pulmonary oedema induced by a piece of chicken M Ranta MRCS (Glasg) DLO A J Cain FRCS B Odutoye FRCS R E Mountain FRCS J R Soc Med 2002;95:404–405
After acute airway obstruction by a foreign body, removal of the offending object generally leads to swift recovery. A rare complication is negative-pressure pulmonary oedema. supraventricular tachycardia. There was no apparent cause such as intercurrent illness, drug therapy, vomiting or diarrhoea. Renal function, plasma sodium and plasma cortisol were all within normal limits, as was 24 h potassium excretion (64 mmol/L at a time when plasma sodium was 2.8 mmol/L). Aldosterone and renin studies were not performed. The patient died after three months and necropsy was not done. COMMENT
This patient had features compatible with sporadic CJD (Box 1). The progressive worsening of hypokalaemia that accompanied his neurological deterioration raised the question whether CJD can affect potassium metabolism. This hypothesis is somewhat weakened by the presence of mild hypokalaemia a year before onset of symptoms. Clinically, the hypokalaemia and its effects were very hard to manage. The possible association with CJD deserves further exploration. I thank Dr Fyaad Ahmed, Dr Andrea Loman and Professor RG Will for their help. Acknowledgments
REFERENCES
1 Will RG, Mathews WB. A retrospective study of Creutzfeldt–Jakob disease in England and Wales 1970–79 1: Clinical features. J Neurol Neurosurg Psychiatry 1984;47:134–40 2 Will RG. Prion related disorders. J R Coll Physicians 1999;33:311–15
CASE HISTORY
A previously healthy man aged 47 choked while eating a piece of boneless chicken breast, and a Heimlich manoeuvre was immediately performed. The apparent airway obstruction was improved but he continued to cough vigorously, producing blood-stained frothy sputum. He also reported increasing dyspnoea and retrosternal pain. On admission to hospital three hours after the incident the patient was still coughing and pulse oximetry showed an oxygen saturation of 92% on room air. On examination the trachea was central; percussion of the chest was dull over the right base and midzone with poor air entry and coarse crackles. No radio-opaque foreign body was visible on chest radiography but there was haziness in all lung fields except for the right middle lobe. Acute airway obstruction by a foreign body was diagnosed and the patient underwent urgent bronchoscopy and rigid endoscopic assessment of the bronchial tree. No foreign body was found, but copious frothy bloody secretions were suctioned from both main bronchi. Despite the appearance of the chest X-ray, the area of the right middle lobe bronchus was endoscopically no different from the remainder of the tracheo-bronchial tree. A rigid oesophagoscopy was also performed, but again no foreign body was retrieved. Oxygen saturation remained around 90% throughout this procedure despite administration of 100% oxygen. When extubation was attempted the patient became restless and was unable to maintain oxygenation. He was reintubated and transferred to the intensive care unit for ventilation. Treatment with intravenous metronidazole and cefuroxime was started. A CT scan of the chest did not reveal any focal lesion but over the next few days oxygenation became increasingly difficult to maintain. The patient had to be ventilated with Department of Otolaryngology, Head and Neck Surgery, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, UK
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Correspondence to: Mr Angus Cain E-mail:
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positive end-expiratory pressure in the prone position and a tracheostomy was performed to assist with bronchial toilet. Recovery was slow, but he was eventually weaned from the ventilator and later decannulated before being discharged home. COMMENT
Pulmonary oedema as a complication of upper airway obstruction in adults was originally reported by Oswalt et al. in 19771. In this series of three cases the causes were upper airway tumour, strangulation and hanging. Since then, negative-pressure pulmonary oedema has been reported mainly by anaesthetists2–4 as a consequence of postoperative laryngospasm. According to one estimate, negative-pressure pulmonary oedema develops in 11% of all patients requiring active intervention for acute upper airway obstruction5. Healthy middle-aged males seem especially prone to this complication2. What is the pathophysiological mechanism of negativepressure pulmonary oedema? A generally accepted cause is excessive negative intrapleural and transpulmonary pressure produced by forceful inspiration against a closed glottis. The negative intrathoracic pressure also increases right-sided cardiac filling, raising pulmonary arterial pressure and thereby pulmonary capillary pressure with transudation into the interstitial and alveolar spaces3–5. The other main factor implicated in the pathophysiology of negative-pressure pulmonary oedema is mechanical disruption of the alveolarcapillary membrane or what is termed ‘stress failure’6. Hypoxia, acidosis and a hyperadrenergic state are also thought to be important1,7,8. Goldenberg et al.9 point to the possible relevance of cardiac anomalies: they found that 50% of patients with negative-pressure pulmonary oedema had such abnormalities compared with 1% of the general population. In the patient reported here, an echocardiogram was not performed. In the published reports there is much variation both in the duration of obstruction that precedes negative-pressure
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pulmonary oedema and in the time between obstruction and onset. Usually the condition develops within minutes but in some instances it has begun up to an hour after clearance of the upper airway obstruction. A suggested explanation for delayed onset is that forced expiration against a closed glottis creates positive intra-alveolar pressures that oppose fluid transudation—a protective effect that is lost after clearance of the blockage2. The recovery of our patient was atypically slow. Negative-pressure pulmonary oedema usually resolves rapidly with short-term ventilatory support, the key principle of treatment being early application of positive pressure to the airway. Adjunctive treatment with steroids, diuretics and bronchodilators has been proposed but their contribution to management is unclear3.
REFERENCES
1 Oswalt CE, Gates GA, Holmstrom FMG. Pulmonary edema as a complication of acute airway obstruction. JAMA 1977;238:1833–5 2 Cascade PN, Alexander GD, Mackie DS. Negative-pressure pulmonary oedema after endotracheal intubation. Radiology 1993;186:671–5 3 McConkey PP. Postobstructive pulmonary oedema—a case series and review. Anaesth Intensive Care 2000;28:72–6 4 Dolinski SY, MacGregor DA, Scuderi PE. Pulmonary hemorrhage associated with negative pressure pulmonary edema. Anesthesiology 2000;93:888–90 5 Tami TA, Chu F, Wildes TO, et al. Pulmonary edema and acute upper airway obstruction. Laryngoscopy 1986;96:506–8 6 Schwartz DR, Maroo A, Malhotra A, et al. Negative pressure pulmonary haemorrhage. Chest 1999;115:1194–7 7 Deepika K, Kenaan CA, Barrocas AM, et al. Negative pressure pulmonary edema after acute upper airway obstruction. J Clin Anesth 1997;9:403–8 8 DeSio JM, Bacon DR. Complete airway obstruction caused by a pseudomembranous cast with subsequent negative pressure pulmonary edema. Anesth Analg 1993;76:1142–3 9 Goldenberg JD, Portugal LG, Wenig BL, Weingarten RT. Negative pressure pulmonary edema in the otolaryngology patient. Otolaryngol Head Neck Surg 1997;117:62–6
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